Interleukin-4-dependent immunoglobulin G1 isotype switch in the presence of a polarized antigen-specific Th1-cell response to the trypanosome variant surface glycoprotein.
This study examines B-cell immunoglobulin (Ig) class-switching events in the context of parasite antigen-specific Th-cell responses in experimental African trypanosomiasis. Inbred mice were infected with Trypanosoma brucei rhodesiense, and the coordinate stimulation of Th-cell cytokine responses and B-cell responses to the trypanosome variant surface glycoprotein (VSG) was measured. The cytokines produced by T cells in response to VSG, at both the transcript and protein levels, were gamma interferon and interleukin-2 (IL-2) but not IL-4 or IL-5. Isotype profiles of antibodies specific for VSG showed that IgG1, IgG2a, and IgG3 switch responses predominated; no VSG-specific IgE responses were detected. To determine whether cryptic IL-4 responses played a role in promoting the unexpected IgG1 switch response, IL-4 knockout mice were infected; the cytokine responses and Ig isotype profiles of IL-4 knockout mice were identical to those of the wild-type control mice except for dramatically reduced IgG1 levels in response to VSG. Thus, these results revealed an IL-4-dependent component of the VSG-driven B-cell Cmu-to-Cgamma1 switch. We speculate that an IL-4 response is mediated primarily by cells other than T lymphocytes since IL-4-secreting but parasite antigen-unresponsive, "background" cells were detected in all infected mice and since infected nude mice also displayed a detectable IgG1 switch response. Overall, our results suggest that B-cell clonal stimulation, maturation, and Ig class switching in African trypanosomiasis may be partially regulated by unusual mechanisms that do not include antigen-specific Th1 or Th2 cells.
Schopf
L R
LR
Department of Bacteriology, University of Wisconsin, Madison 53706, USA.
Filutowicz
H
H
Bi
X J
XJ
Mansfield
J M
JM
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood*; D002478:Cells, Cultured; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D018417:Th1 Cells / Q000276:immunology*; D016833:Trypanosoma brucei rhodesiense / Q000276:immunology*; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000276:immunology*
D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D007376:Interleukin-2; D012333:RNA, Messenger; D014643:Variant Surface Glycoproteins, Trypanosoma; D015847:Interleukin-4; D007371:Interferon-gamma